Systems and methods for matching and imaging tissue characteristics

ABSTRACT

Systems and methods for matching a characteristic of multiple sectors of a moving tissue to verify an overlap thereof are disclosed herein. In an exemplary method, tissue data for at least a first sector and a second sector of a moving tissue is acquired. A characteristic of at least a portion of the first and second sectors is estimated from the acquired tissue data, and the estimated characteristics are matched to verify whether a portion of the first sector overlaps with a portion of the second sector. Estimating can include estimating a displacement such as an axial displacement and/or lateral displacements. Estimating can further include estimating a strain, a velocity, a strain rate and/or a stiffness or equivalent.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation application of U.S. application Ser. No. 13/848,436, filed Mar. 21, 2013, which is a continuation application of U.S. application Ser. No. 13/019,029, filed on Feb. 1, 2011, now U.S. Pat. No. 8,428,687, issued on Apr. 23, 2013, which is a continuation-in-part of International Application Serial No. PCT/US2009/052563 entitled “Systems and Methods for Matching and Imaging Tissue Characteristics”, filed on Aug. 3, 2009, which claims priority to U.S. Provisional Application No. 61/085,709 entitled “Motion Matching for Imaging and Estimation of Tissue Displacement”, filed on Aug. 1, 2008, U.S. Provisional Application No. 61/086,112 entitled “Elastocardiography System for Automated Detection of Medical Conditions in a Subject”, filed on Aug. 4, 2008, and U.S. Provisional Application No. 61/108,470 entitled “Electromechanical Wave Imaging for Detection of Ischemia”, filed on Oct. 24, 2008, each of which are incorporated by reference in their entireties herein and from which priority is claimed.

STATEMENT REGARDING FEDERALLY-SPONSORED RESEARCH

This invention was made with government support under R01 EB006042 and R21 HL096094 awarded by the National Institutes of Health. The government has certain rights in the invention.

BACKGROUND

Field

The present application relates to systems and methods for anatomical and functional matching and imaging of tissue characteristics.

Background Art

Electrical mapping of the heart has emerged as an important tool for treatment monitoring of arrhythmias such as ventricular tachycardia. The map of local timings of electrical activation in the ventricle can identify abnormally conducting regions and guide radio frequency (RF) ablation treatments. Currently available clinical mapping systems are, however, invasive, since they require catheterization for introduction into the heart chamber. Therefore, electrical mapping cannot be performed for early detection of diseases or follow-up of chronic diseases such as heart failure.

Electromechanical Wave Imaging (EWI) has recently been introduced as a non-invasive, inexpensive, ultrasound-based modality, which can potentially map the electrical activation of the heart transmurally along various echocardiographic planes. This imaging modality is based on the measurement of small, transient deformations occurring in the myocardium a few milliseconds after, but following similar patterns as, the electrical activation. More specifically, after the action potentials reach the myocytes, the latter undergo depolarization followed by an uptake of calcium, which triggers contraction a few milliseconds later. Therefore, by measuring the onset of this contraction, the activation pattern across the entire myocardium can be mapped.

Over the past two decades, several methods have been developed for measuring deformations using ultrasound-based methods. Two-dimensional speckle-tracking-based motion estimation techniques have been implemented on clinical systems. Different approaches based on B-Mode or radio-frequency (RF) speckle tracking, or phase-tracking techniques have also been proposed in the literature for myocardial contractility assessment. Recently, open architecture ultrasound systems enabled motion estimation at very high effective RF-frame rates of standard echocardiographic views. The full view of the heart is divided into five to seven sectors acquired at very high frame rates and a full view cine-loop is then reconstructed via electrocardiogram (ECG)-gating. Such high frame rates and the RF phase information increase the estimation quality and thus the reliability of two-dimensional displacement and strain mapping.

The increase in the frame rate did not only allow a better precision in the RF-based motion estimation, but also achieved a temporal resolution on the same time scale as that of the electrical propagation. More specifically, it allowed the detection of transient phenomena that occur during both isovolumic phases. For example, it was possible to identify the mechanical waves in the myocardial wall occurring when the valves open and close. Incremental displacements waves generated by the early contraction of myocytes, i.e., the Electromechanical Wave (EMW), have been depicted on EWI ciné-loop and images, and their correlation with the electrical activation velocity and pacing scheme have been verified. More recently, the EMW was reproduced in simulations and shown to be correlated with simulated and experimental electrical activation patterns.

Alternative methods for assessment of local electrical properties in vivo involve the use of electrode arrays, either by mounting an electrode sock around the heart through open-heart surgery to map the epicardial activation or by using electrode catheters. Newly developed non-invasive techniques based on heart models provided fully three-dimensional activation sequences. A method based on magnetic resonance (MR) tagging has also been proposed, where the subepicardial contraction sequence was mapped and compared to the electrical activation maps obtained with an epicardial electrode sock.

ECG-gating methods are common in biomedical imaging technologies to achieve frame-rate that are sufficient to obtain an accurate depiction of the cardiac motion either in two or three dimensions. It is useful, for instance, when imaging the heart or the cardiovascular system using computed tomography, magnetic resonance imaging, or nuclear imaging.

Though previous efforts have obtained high frame rates using ECG gating, for the analysis of diseases such as ventricular tachycardia, the ECG may not be regular. For example, when atrio-ventricular dissociation occurs, the atria and ventricles follow different rhythms, which may compromise the use of the ECG for co-registration of adjacent sectors. Accordingly, there is a need in the art for a non-invasive imaging technique that is not reliant on independent measurements of the electrical activity of the subject tissue.

SUMMARY

Systems and methods for matching a characteristic of multiple sectors of a moving tissue to verify an overlap thereof are disclosed herein. In an exemplary method, tissue data for at least a first sector and a second sector of a moving tissue is acquired. A characteristic of at least a portion of the first and second sectors is estimated from the acquired tissue data, and the estimated characteristics are matched to verify whether a portion of the first sector overlaps with a portion of the second sector. Estimating can include estimating a displacement such as an axial displacement and/or lateral displacements. Estimating can further include estimating a strain, a velocity, a strain rate and/or a stiffness or similar measures.

The method can further include determining a time delay between the matched characteristics, which can be utilized to form an image of the matched characteristic in at least the overlapping portion of the sectors.

In some embodiments, an image can be formed from a one-, two-, three-, or four-dimensional image of the target tissue. Further, in some embodiments, estimating the displacements of the target tissue can be performed using a speckle-tracking technique. A method in accordance with the disclosed subject matter can also include acquiring electrical activity data from the target tissue, and determining a correspondence between the electrical activity and the estimated characteristic of the sectors.

An exemplary system for matching a characteristic of multiple sectors of a moving tissue to verify an overlap thereof in accordance with the disclosed subject matter includes a computer readable medium storing program instructions, and a processor adapted to receive tissue data for at least a first sector and a second sector of a moving tissue. The processor is operatively connected to the computer readable medium and configured to execute the stored program instructions, and is further configured such that upon execution of the stored program instructions, the processor estimates a characteristic of at least a portion of the first and second sectors from the acquired data, and matches the estimated characteristics. The processor can further determine a time delay between the matched characteristics, and form an image of the matched characteristics in at least the overlapping portion of the sectors utilizing the determined time delay.

A system in accordance with the disclosed subject matter can further include a data acquisition device for acquiring data from two or more sectors of the tissue. The data acquisition device can be an ultrasound device and can be capable of acquiring frames of data a rate of at least 50 to 10000 frames per second. The data acquisition device can also be another imaging modality, such as an MRI or CT device. The system can further include an electrical detection device configured to detect an electrical signal propagating through the tissue, which can be an electrocardiographic device.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are incorporated and constitute part of this disclosure, illustrate some embodiments of the disclosed subject matter.

FIG. 1 illustrates a system for imaging the displacement of tissue in accordance with an exemplary embodiment of the disclosed subject matter.

FIG. 2 illustrates a method for imaging the displacement of tissue in accordance with an exemplary embodiment of the disclosed subject matter.

FIG. 3A illustrates an example of a method utilizing a two sectors acquired in accordance with an exemplary embodiment of the disclosed subject matter.

FIG. 3B illustrates a graph depicting the displacements of the two sectors illustrated in FIG. 3A over time, in accordance with an exemplary embodiment of the disclosed subject matter.

FIG. 4A is a graph illustrating the incremental displacements estimated in two sectors at the overlapping portion during two different cardiac cycles in a normal, open-chest, canine heart.

FIG. 4B illustrates the correlation coefficient in based on data taken from a normal, open-chest, canine heart.

FIG. 5A illustrates a 3D rendering of a parasternal four-chamber view of a heart.

FIG. 5B illustrates a 2D parasternal four-chamber view of a heart prepared in accordance with an exemplary embodiment of the disclosed subject matter.

FIG. 5C illustrates a 3D rendering of parasternal two-chamber view of a heart.

FIG. 5D illustrates the corresponding 2D parasternal two-chamber view of a heart prepared in accordance with an exemplary embodiment of the disclosed subject matter.

FIG. 6 is a graph of the temporal variation of the incremental strains along three points in the septum in accordance with an exemplary embodiment of the disclosed subject matter.

FIGS. 7A-7F illustrates the propagation of incremental displacement in the four-chamber view over six image frames generated in accordance with an exemplary embodiment of the disclosed subject matter.

FIGS. 7G-7L illustrates 2D strain images corresponding to the incremental displacement images of FIG. 7A generated in accordance with an exemplary embodiment of the disclosed subject matter.

FIGS. 8A-8I illustrates 2D strain images of electromechanical wave propagation in a normal heart under sinus rhythm in the parasternal two-chamber view in accordance with an exemplary embodiment of the disclosed subject matter.

FIGS. 9A-9D illustrates isochrones of the two different dogs in the two- and four-chamber view showing the time of arrival of the electromechanical wave in accordance with an exemplary embodiment of the disclosed subject matter.

FIGS. 10A-10F show the evolution of the electromechanical wave with different levels of ischemia in accordance with an exemplary embodiment of the disclosed subject matter.

FIG. 10G illustrates the evolution of the electromechanical wave after reperfusion in accordance with an exemplary embodiment of the disclosed subject matter.

FIG. 10H illustrates the evolution of the P-V loop with the occlusion level in accordance with an exemplary embodiment of the disclosed subject matter.

FIG. 10I illustrates pathological cross-section taken after reperfusion in accordance with an exemplary embodiment of the disclosed subject matter.

FIGS. 11A-11I illustrate a bi-plane view of a heart under different left anterior descending coronary artery occlusion levels in accordance with an exemplary embodiment of the disclosed subject matter.

FIGS. 12A-12C illustrate electromechanical strain maps in accordance with an exemplary embodiment of the disclosed subject matter.

FIGS. 13A-13C illustrate images of a pulse wave propagating through the abdominal aorta of a healthy human volunteer in accordance with an exemplary embodiment of the disclosed subject matter.

FIGS. 14A-14F illustrate electromechanical wave imaging of a patient undergoing cardiac resynchronization therapy in accordance with an exemplary embodiment of the disclosed subject matter.

FIG. 15 illustrates a 3D electromechanical strain image in accordance with an exemplary embodiment of the disclosed subject matter.

FIGS. 16A-16E illustrate the propagation of the electromechanical wave from a pacing lead location in the basal region of the lateral wall in accordance with an exemplary embodiment of the disclosed subject matter.

FIG. 16F illustrates the activation of the electrocardiogram as the electromechanical wave propagates in accordance with an exemplary embodiment of the disclosed subject matter.

FIGS. 17A-17D illustrate isochronal maps of four different pacing schemes in both anterior and posterior views in accordance with an exemplary embodiment of the disclosed subject matter.

FIG. 17E illustrates an isochronal map in both anterior and posterior views during sinus rhythm in accordance with an exemplary embodiment of the disclosed subject matter.

FIG. 18 illustrates the electromechanical wave onset time versus the time of electrical activation for five different pacing schemes in accordance with an exemplary embodiment of the disclosed subject matter.

FIG. 19A illustrates the propagation of electromechanical waves in all four cardiac chambers of a healthy human subject in accordance with an exemplary embodiment of the disclosed subject matter.

FIG. 19B illustrates the corresponding isochronal representation of the electromechnical wave in FIG. 19A in accordance with an exemplary embodiment of the disclosed subject matter.

DETAILED DESCRIPTION

The systems and methods described herein are useful for matching a characteristic of a moving tissue in two or more sectors of the tissue and imaging the same. Although the description is focused on the example of myocardial tissue analysis, the systems and methods herein are useful for motion-matching in other tissues, such as the aorta or the liver.

The techniques described herein makes use of data acquisition equipment, e.g., ultrasound, MRI, CT, or other imaging devices, to acquire motion data in multiple sectors of a tissue undergoing periodic motion, e.g., motion data of a heart during the cardiac cycle. That data is then reconstructed into one-, two-, three or four-dimensional images by matching up the data in overlapping areas of the sectors and further by accounting for the time delay between the data acquired in different sectors. By utilizing such a technique the systems and methods described herein can be used to produce a composite image of the tissue.

FIG. 1 illustrates a system 100 for matching a characteristic of two or more sectors of a moving tissue to verify whether any portions thereof overlap in accordance with an exemplary embodiment of the disclosed subject matter. The system 100 can comprise a data acquisition device 110, e.g., an ultrasound, MRI, CT or other device, for acquiring tissue data for at least a first sector and a second sector of said moving tissue 120, e.g., a heart, liver, blood, or other tissue. The tissue 120 can be separated into two or more sectors 1, 2 such that each sector shares an overlapping portion 3 with another sector (illustrated in FIG. 3(a)). The overlapping portion 3 does not need to be contiguous with other portions of sectors 1, 2. In one embodiment, tissue 120 can be divided into five to seven sectors. FIG. 1 illustrates an exemplary embodiment wherein the characteristic matching is conducted on a patient P non-invasively. Specific examples discussed below were performed on open-chested dogs and on humans in vivo.

The data acquisition device 110 can be composed of a scanner 111 and a probe 112, as is understood in the art and discussed in U.S. patent application Ser. No. 11/433,510, the entire contents of which is incorporated by reference herein. Further, in exemplary embodiments involving myocardial tissue the data acquisition device 110 can be capable of acquiring data at a sufficiently high rate such that it can capture an electromechanical wave propagation through the myocardial tissue. In one exemplary embodiment, the data acquisition device 110 can acquire data at a rate of at least 50 frames per second (fps). Preferably the data acquisition device 110 can acquire data at a rate of 1,000-10,000 fps. In one specific embodiment, the data acquisition device 110 is an Ultrasonix RP system with a 3.3 MHz phased array capable of acquiring image data at a rate from 390 to 520 fps. The data acquisition device 110 can also be configured to acquire data using an automatic composite technique, as discussed in Wang et al., “A composite high-frame-rate system for clinical cardiovascular imaging,” Ultrasonics, Ferroelectrics and Frequency Control, IEEE Transaction on, vol. 55, 2008, pp. 2221-2233, which is incorporated by reference herein in its entirety. It is understood that a larger number (and hence smaller size) of sectors 1, 2 will directly contribute to an increase in the acquisition rate achievable by the data acquisition device 110 for a given tissue 120.

The image acquisition device 110 is operatively connected to a computer system 130 which is comprised of a processor 131 and a memory 132 operatively connected to the processor 131. The processor 131 is adapted to receive tissue data for at least the first and second sectors 1, 2 of the moving tissue 120. The computer system 130 also includes a computer readable medium 133, e.g., a hard disk drive, CD, etc., which is operatively coupled to the processor 131 and the memory 132. The computer readable medium 133 stores program instructions to be executed by the processor 131, utilizing the memory 132, to estimate a characteristic of at least a portion of the first sector 1 and a characteristic of at least a portion of the second sector 2. The processor 131 further executes the stored program instructions to match the estimated characteristic of the portion of the first sector 1 with the estimated characteristic of the portion of the second sector 2.

It will be understood by those skilled in the art that sectors 1, 2 can be chosen such that they share overlapping portion 3 prior to the execution of the program instructions by processor 131. The presently disclosed subject matter also envisions that sectors 1, 2 can be chosen without foreknowledge of the existence, location or particular dimensions of overlapping portion 3. In either scenario matching the portion of the sectors 1, 2 will verify whether those portions form overlapping portion 3.

The processor 131 can be further configured to determine a time delay between the matched characteristic of the portion of the first sector 1 and the matched characteristic of the portion of the second sector 2. The processor 131 can utilize the time delay determination to form an image of the matched characteristic of the portion of the first sector 1 and the matched characteristic of the portion of the second sector 2.

The same or a different computer readable medium 133 can be used to store the image of the matched characteristic of tissue 120 and further can be used to store the acquired data. The computer system 130 can further be comprised of a visual display unit 134, e.g., a computer monitor, for displaying the composite image, and the series of images if desired. The computer system 130 can also be connected to input device 114, e.g., a keyboard.

The computer system 130 can be any standard desktop computer or other suitable computing system. In one embodiment, for example in connection with the below described experiment, the computer system 130 is a 120-node Linux cluster, each node composed of two AMD Operon Model 2222 CPUs (two cores per CPU), 8 GB RAM, and a 160 GB SATA hard disk drive operating at 7200 RPM.

The system 100 can further be comprised of an electrical detection device 140, e.g., an electrocardiographic device (ECG). As illustrated in FIG. 1, the electrical detection device 140 can be connected to the tissue 120 to measure the electrical activity therein. The electrical detection device 140 can be further operatively connected to computer system 130, but could also be connected to a different computer system (not shown), if desired.

FIG. 2 illustrates a method 200 for matching a characteristic of multiple sectors 1, 2 of a moving tissue 120 in accordance with an exemplary embodiment of the disclosed subject matter. The method 200 comprises acquiring 210 tissue data for at least a first sector 1 and a second sector 2 of the moving tissue 120, e.g., a heart, aorta, liver, blood or other tissue. The acquired data 210 can be acquired by a data acquisition device 110, e.g., an ultrasound, MRI, CT or other device capable of acquiring tissue data. As discussed above, the tissue data can be acquired 210 at a rate of 50-10,000 fps.

The method 200 further comprises estimating 220 a characteristic of at least a portion of the first sector 1 and a characteristic of at least a portion of the second sector 2 from the acquired tissue data. The estimated characteristic of the portion of the first sector 1 and the portion of the second sector 2 are matched 230. As discussed above, the matching 230 verifies whether the portion of the first sector 1 and the portion of the second sector 2 comprise overlapping portion 3.

Also as noted above, skilled persons will understand the techniques described herein are useful whether sectors 1, 2 are chosen such that they share overlapping portion 3 or whether sectors 1, 2 are chosen without such foreknowledge. Further, the overlapping portion 3 does not have to be contiguous with other portions either of sectors 1, 2. In one exemplary embodiment, the target tissue 120 can be divided into five to seven sectors each sharing at least one overlapping portion 3 with another sector. In the same or another exemplary embodiment, the target tissue 120 was chosen to have five sectors, each comprised of 16 radio frequency (RF) lines (or “RF beams”), and the acquisition 210 was performed at 389 fps using an automatic composite imaging technique. For each sector, approximately three heart cycles were recorded and three RF beams comprised the overlapping portions 3 shared by adjacent sectors. Thus, for this exemplary embodiment, the full-view image of target tissue 120 comprised of 65 RF lines.

In one embodiment, the estimation 220 comprises estimating a displacement. The estimation 220 can also comprise estimating a strain, a velocity, a strain rate, and/or a stiffness. Indeed, it is understood the disclosed subject matter can comprises estimating 220 other characteristics of tissue indicative of tissue motion. Further the estimation 220 can be performed for each sector 1, 2 using techniques well known in the art, e.g., a speckle-tracking technique. Where the characteristic estimated 220 is displacement, it can comprise axial and/or lateral displacement. In one embodiment, the estimation 220 can be a one-dimensional (1D) axial incremental displacement estimation using an RF-based cross-correlation method, as is known in the art and described in U.S. patent application Ser. No. 11/697,573, the entirety of which is incorporated by reference herein. In one embodiment, the estimation 220 is performed with a window size of 4.6 mm and an 80% overlap.

In the same or another embodiment, estimation 220 can comprise estimating the two-dimensional (2D) displacement. In one exemplary embodiment, to determine the 2D displacement, first a 16:1 linear interpolation scheme between two adjacent original RF signal segments can be employed to improve the lateral resolution. Second, the cross-correlation between reference RF signal segment and the candidate RF signal segments can be performed. Third, the RF signal segment in the comparison frame that yielded the highest 2D correlation coefficient can be considered the best match with the RF signal segment in the reference frame. One-dimensional cosine interpolation along each direction can then be applied around the initial maximal value of the cross-correlation function in order to increase the precision of the peak detection. Thus, the lateral displacement, i.e., Δl, denotes the estimated motion occurring between the reference RF signal segment and its best comparison frame match. The axial displacement, Δa, will be the estimated axial time-shift, or displacement, along the matched RF signal segment. Hence, a kernel in a 2D search yields the two orthogonal, in-plane components of the displacement simultaneously, i.e., (Δl, Δa). The lateral decorrelation due to axial motion reduces the accuracy of the lateral displacement estimation. Therefore, the correction in axial displacement estimation, or recorrelation, has to be performed to reduce this decorrelation noise. In myocardial elastography, a recorrelation method can be implemented by shifting RF signal segments according to the estimated axial displacement in the comparison frame, prior to the second lateral displacement estimation. The recorrelation strategy can also be utilized to correct the lateral displacement prior to the second axial displacement estimation. Once both lateral and axial displacement have been estimated it is possible to obtain radial and circumferential displacements. Since the myocardium can be segmented, the radial and circumferential directions can be defined as the directions normal and parallel to the tangent of the myocardial surfaces. When the epicardial and endocardial surfaces are not parallel, their tangential directions can be averaged.

The method 200 can further comprise determining 240 the time delay between the matched characteristic of the portion of the first sector 1 and the matched characteristic of the portion of the second sector 2. An image of the matched characteristic of the portion of the first sector 1 and the matched characteristic of the portion of the second sector 2 can be formed 250 utilizing the determination 240 of the time delay. The image can be formed 250 as either a one-, two-, three- or four-dimensional image. The image formed 250 can also be over the entirety of sectors 1, 2, thus creating a composite image of some or all of the sectors for which data was acquired 210. Multiple images formed 250 at different times may be sequenced over time to create a video of the moving tissue across the desired sectors 1, 2. For example, where the matched characteristic is the one-dimensional displacement, that displacement can be estimated 220 and matched 230 over time to form 250 a two-dimensional image, e.g., a video. In another example, an axial displacement can be estimated 220 and matched 230 in three-dimensions over time to form 250 a four-dimensional image, e.g., a video.

FIG. 3A illustrates an example of method 200 utilizing two sectors 1, 2 acquired 210 in accordance with an exemplary embodiment of the disclosed subject matter. As illustrated in FIG. 3, sector 1 and sector 2 share an overlapping portion 3. A characteristic, here displacement, is estimated 220 for each of sector 1 and sector 2. As FIG. 3B illustrates, the displacement of each sector k can be expressed as function D_(k)(r,θ,t), where displacement D_(k) is a function of the depth r, angle θ, and time t. Thus, the displacement estimate for sector 1 (D₁) and sector 2 (D₂) can be computed at each point (r,θ).

FIG. 3B illustrates a graph 310 depicting the displacement functions D₁ and D₂ over time at point (r, θ) located in overlapping region 3. The displacements functions D₁ and D₂ should be identical for overlapping region 3, thus the matching 230 is accomplished by matching corresponding displacements found in both D₁ and D₂. The acquiring 210 of sectors happens sequentially, so it follows that the corresponding displacements found in D₁ and D₂ will be offset by some time period t. Graph 310 illustrates that characteristic (in this example displacement) 311 of D₁ and characteristic (in this example displacement) 312 of D₂ are corresponding characteristics that have been acquired at two different times, once in sector 1 and once in sector 2.

Once displacement 311 and displacement 312 have been matched 230, the time delay between data acquisitions 210 is determined by calculating the difference in the time of occurrence of 311 and 312. In FIG. 3B, the displacements D₁ and D₂ are offset by time period t₁.

FIG. 3B further illustrates the electrocardiogram (ECG) for sector 1, graphed over time. As can be seen, the ECG for sector 1 shows a spike in electrical activity 313 corresponding to displacement 311 of D₁, thus confirming the accuracy of motion data as a representation of the electrical activity of the target tissue 120, in this example a heart. FIGS. 3A-3B illustrate that the matching 230 and the time delay determination 240 can be performed visually, e.g., by graphing the characteristics over time. However, the matching 230 and time delay determination 240 can also be performed using the numerical approach discussed below.

In the example of a heart it can be assumed that the heart has a periodic motion, thus the same information is acquired twice in the overlapping regions at different times. Accordingly, in an exemplary embodiment where the target tissue 120 is heart tissue, the periodicity of that heart implies that the following equation holds for all sectors k, depths r, angles θ, and times t:

D _(k)(r,θ,t)=D _(k)(r,θ,t+nT),  (1)

where, as above, D_(k) denotes the displacement estimate in sector k, T denotes one heart cycle duration and n is an integer. Each sector k+1 is delayed with respect to the preceding sector k and the following equation holds for overlapping sectors, denoted by θ′:

$\begin{matrix} \begin{matrix} {{D_{k + 1}\left( {r,\theta^{\prime},t} \right)} = {D_{k}\left( {r,\theta^{\prime},{t + {nT} + t_{k}}} \right)}} \\ {= {{D_{k}\left( {r,\theta^{\prime},{t + t_{k}}} \right)}.}} \end{matrix} & (2) \end{matrix}$

Forming 250 the full-view image of all sectors k is equivalent to estimating t_(k) for all k. This is achieved by finding the time associated with the peak of the cross-correlation function, also known as a motion-matching algorithm:

$\begin{matrix} {t_{k} = {\underset{r,t^{\prime}}{argmax}{\int_{- \infty}^{+ \infty}{{D_{k + 1}\left( {r,\theta^{\prime},t} \right)}{D_{k}\left( {r,\theta^{\prime},{t + t^{\prime}}} \right)}{{t}.}}}}} & (3) \end{matrix}$

Equation (3) can be implemented numerically and the true peak approximated using cosine interpolation. One of the main advantages of the characteristic- (or motion-) matching technique discussed herein is that the cross-correlation method also provides a correlation coefficient that indicates the quality of the sector matching. In one embodiment, data can be acquired 210 for two to three heart cycles per sector, it is then possible to select the best combination out of multiple heart cycles. For example, if two heartbeats were acquired 210 per sector over seven sectors, it would be possible to choose among 128 combinations of heart cycles.

It is understood that the above recited techniques, including the equations, would be useful in implementing the disclosed subject matter for tissues other than the heart, such as the liver, blood, or any tissue undergoing periodic motion.

FIG. 4A is a graph illustrating the incremental displacements estimated 220 in sectors 1 and 2 at overlapping portion 3 based on data acquired in sectors 1 and 2 during two different cardiac cycles in a normal, open-chest, canine heart. FIG. 4A shows good matching between the temporal evolution of incremental displacements obtained in overlapping RF beams during the two different heartbeats. The top line in FIG. 4A represents the ECG.

FIG. 4B displays the temporal correlation coefficient along the same RF beam. As with FIG. 4A, FIG. 4B illustrates the correlation coefficient in based on data taken from a normal, open-chest, canine heart, where LV is the left ventricle and RV is the right ventricle. A correlation coefficient close to 1 is obtained at the level of the myocardium, while the correlation was low in the blood cavities (due to the blood flow and low scattering) and in the surrounding ultrasound gel (which does not undergo periodic motion).

FIG. 5A illustrates a 3D rendering of a parasternal four-chamber view of a heart. FIG. 5B illustrates the corresponding 2D parasternal four-chamber view of a heart prepared in accordance with the techniques described herein. In FIGS. 5A-5B both the right (RV) and left ventricle (LV) cavities are visible, along with the septum (green), the lateral wall (light shading) and the right ventricular wall (dark shading).

FIG. 5C illustrates a 3D rendering of parasternal two-chamber view. FIG. 5D illustrates the corresponding 2D parasternal two-chamber view of a heart prepared in accordance with the techniques described herein. In FIGS. 5C-5D, the left ventricle cavity is visible, along with the posterior and anterior walls. In both views (FIGS. 5B and 5D), the axial direction coincides most of the time with the radial direction.

As noted above, the estimating 220 the characteristic can comprise estimating a strain. The strain can be defined in terms of the gradient of the displacement and two-dimensions, in-plane displacement can be written as u=u_(x) e _(x)+u_(y) e _(y), where u_(x) and u_(y) are lateral and axial displacements, respectively. The e _(x) and e _(y) are unit coordinate base vectors in lateral and axial directions, respectively. The 2D displacement gradient tensor, ∇u, can then be defined as

$\begin{matrix} {{\nabla\underset{\_}{u}} = {\begin{bmatrix} {\frac{\partial u_{x}}{\partial x}\frac{\partial u_{x}}{\partial y}} \\ {\frac{\partial u_{y}}{\partial x}\frac{\partial u_{y}}{\partial y}} \end{bmatrix}.}} & (4) \end{matrix}$

The 2D Lagrangian finite strain tensor, E, is defined as

E=½(∇ u +(∇ u )^(T)+(∇ u )^(T) ∇u ),  (5)

where (∇u)^(T) is the transpose of ∇u. Lateral and axial strains will be diagonal components of E, i.e., E_(xx) and E_(yy), respectively. In order to improve the signal-to-noise ratio (SNR) a least-squares strain estimator (LSQSE) can be used. The LSQSE can reduce the noise from the gradient operation through a piecewise linear curve fit to the displacement. A larger lateral kernel, together with the recorrelation method, improves the quality of the estimated lateral strain and renders it comparable to the estimated axial strain.

As noted above, the method 200 can further comprise forming 250 an image of the characteristic of the tissue 120, which as discussed above can be the displacement, strain, velocity, strain rate, stiffness or other characteristic arising from periodic motion. Thus, a strain, velocity, strain rate, stiffness or other characteristic image can be formed 250 in one- to four-dimensions.

FIG. 6 is a graph of the temporal variation of the incremental strains along three points in the septum in the vicinity of the QRS complex (composed of the Q-wave, R-wave and S-wave, illustrated on the ECG line in FIG. 6). The location of the three points can be seen in the insert of FIG. 6, showing left, center and right dots representative of the location of strain measurements on a 2D image of the strain generated as detailed above. Two waves can be identified in FIG. 6: 1) the electromechanical wave (EMW) front defined by the point at which the incremental strains change sign and 2) a mechanical wave (the dashed circle) occurring when the mitral valve closes later and that oscillates both in time and space. The second wave travels from base to apex while the EMW is initiated at the endocardial surface of the septum and travels towards the base and the apex.

In accordance with the principles of the disclosed subject matter an experiment was conducted, with the approval of the Institutional Animal Care and Use Committee at Columbia University, on five mongrel dogs of either sex, ranging from 23 to 32 kg in weight. The dogs were anesthetized with an intravenous injection of thiopental (10-17 mg/kg). The dogs were mechanically ventilated with a rate- and volume-regulated ventilator on a mixture of oxygen and titrated isoflurane (0.5-5.0%). Morphine (0.15 mg/kg, epidural) was administered before surgery, and lidocaine (50 micrograms/kg/hr, intravenous) was used during the whole procedure. To maintain blood volume, 0.9% saline solution was administered intravenously at 5 mL/kg/hr. Each animal was positioned supine on a heating pad.

Standard limb leads were placed for surface electrocardiogram (ECG) monitoring. A solid state pressure transducer catheter (in this example one by Millar Instruments, Houston, Tex.) was inserted into the left-ventricular cavity via the left carotid artery, the aortic root and across the aortic valve. Oxygen saturation of the blood, and peripheral blood pressure were monitored throughout the experiment.

The chest was opened by lateral thoracotomy using electrocautery. After removal of the pericardium, a customized constrictor and a flow probe (in this example one provided by Transonic Systems, Inc., USA) were positioned immediately distal to the first diagonal of the left anterior descending (LAD) coronary artery to induce graded occlusion—and thus variable ischemic levels—at 20% increments of the initial coronary blood flow.

A total of twelve piezoelectric crystals (provided by Sonometrics Corp., Canada) were then implanted in the left ventricular wall. For endocardial and mid-wall crystals, an 18G (18 gauge) needle was used for insertion. All crystals were maintained in position after placement using silk sutures.

Echocardiography was performed at each occlusion level. Forty-five minutes after complete occlusion, the LAD was reperfused. It was then excised and sectioned in 1 cm transverse slices to perform pathology. The sliced heart sections were immersed in a 1% Triphenyltetrazolium chloride (TTC) solution and incubated at 37° C. for 1.5 hours. The sections were then fixed in a 10% formalin solution for 30 minutes. A pale region indicated the site of infarction, while the stark color represented the viable cardiac muscle.

FIGS. 7A-7F illustrate the propagation of incremental displacement in the four-chamber view over six image frames formed 250 during the above-described canine experiment. As illustrated in the side bar in FIGS. 7A-7F light shading indicates movement (displacement) up and dark shading indicates movement (displacement) down, while RV, IVS, LV, and LAT respectively denote right ventricle cavity, interventricular septum, left ventricle cavity and free wall (lateral wall). Therefore, a contracting heart will be mapped in dark shading at the septum and right ventricular wall and in light shading at the lateral wall. FIG. 7A-7F illustrate the corresponding displacement patterns propagating from base to apex in the septum and lateral wall, and propagation of downward motion in the right ventricular wall. The arrows in FIGS. 7A-7F highlight some areas where notable displacement can been seen.

FIGS. 7G-7L illustrate 2D strain images generated 250 during the above-described canine experiment. As discussed above, a least-square strain estimator (LSQSE) was then applied on the incremental displacement data, providing the incremental strain information. As illustrated in the side bar in FIGS. 7G-7L, light shading indicates thickening while dark shading indicates thinning. In regions where the axial direction coincides mainly with the radial direction, contraction will be mapped as thickening of the myocardium. More specifically, two activation sites at the mid-basal level are visible approximately 30 ms after the Q-wave in both the left endocardium of the septum and in the endocardium of the lateral wall (indicated by the dark shaded arrows in the 31.60 ms frame). This is a thickening wave that travels towards both the base and the apex. At approximately 40 ms, a thickening wave becomes visible in the right ventricular wall (white arrow), which travels principally towards the base. Noticeably, 60 ms after the onset of the Q-wave, the basal parts of the three walls are still thinning (light arrows in 61.54 ms frame). In the region where the axial direction matches the longitudinal cardiac coordinate, circled in the 61.54 ms frame, shortening, rather than thickening, is observed.

FIGS. 8A-8I illustrate 2D strain images of electromechanical wave propagation in a normal heart under sinus rhythm in the parasternal two-chamber view, with LV, ANT and POST respectively denoting left ventricle cavity, anterior wall, and posterior wall. As illustrated in FIG. 8, approximately 12 ms after the onset of the QRS, excitation of the posterior wall endocardium begins (green arrow in the 12.68 ms frame). It then propagates both towards the base and the apex. A few milliseconds later, the anterior wall begins to thicken (white arrow in the 22.33 ms frame). The myocardium is almost completely mechanically activated 45 ms after the onset of the QRS; thinning of portions of the base are still visible. The bottom row of FIG. 8 illustrates that the mitral valve closing generates an oscillating wave (light circle), different in nature from the EMW, that emanates from the base and travels towards the apex in the posterior wall.

FIGS. 9A-9D illustrate isochrones of the two different dogs in the two- and four-chamber view showing the time of arrival of the EMW. As illustrated in FIG. 9 the propagation patterns in the two dogs are not identical, but show similar regions of early depolarization and a propagation emanating from those regions to apex and base. The dark circles indicate the regions where the activation times correspond to shortening rather than thickening. This aforementioned EMW propagation is disrupted when, as illustrated in FIG. 8 and discussed above, the mitral valve closes a few milliseconds after the R-wave, approximately at 45 ms.

As discussed above, the techniques described herein are particularly advantageous to imaging cardiac tissue suffering from one or more irregularities, such as ischemia. As a part of the above-described experiment the left anterior descending (LAD) coronary artery was subsequently partially occluded, the coronary flow steadily reaching 80, 60, 40, and 20% of its initial value. Each occlusion increment was sustained for approximately one hour. The LAD was finally completely occluded. Twenty minutes after each occlusion, and over a twenty minute period, the heart was imaged in both the two- and four-chamber views.

FIGS. 10A-10F show the evolution of the EMW with different levels of ischemia, representing no occlusion, 20%, 40%, 60%, 80% and finally 100% occlusion in FIG. 10F. The time at which the images in FIGS. 10A-10F are displayed corresponds to the time at which the activated region covered the largest portion of the myocardium, i.e., immediately preceding the closing of the mitral valve. FIGS. 10D-10F illustrate the ischemic region (light circle), which can be easily identified as the region through which the EMW cannot propagate. Comparison to FIGS. 10A-10C indicates that the ischemic region is visible when the LAD is occluded at 60% and beyond. The ischemic region appears to grow with the occlusion level until it reaches a maximum size at 100% occlusion. After reperfusion, illustrated in FIG. 10G, the size of the ischemic region in the posterior wall decreases.

FIG. 10H illustrates the evolution of the P-V loop with the occlusion level. The presence of acute ischemia was assessed with pathology, after reperfusion, illustrated in FIG. 10I. TTC is used to stain non-viable tissue, which generally spans a smaller region than the ischemic tissue. Reperfusion accentuates the size of this non-viable region. The slice shown in FIG. 10I is approximately at 3 cm from the apex.

FIGS. 11A-11I illustrate a bi-plane (two-chamber+four-chamber) view of the same heart under different LAD coronary artery occlusion levels: normal (FIGS. 11A-11C), 60% occlusion (FIGS. 11D-11F) and 100% occlusion (FIGS. 11G-11I). The ischemia is visible in the anterior, posterior and lateral wall near the apex at 60% occlusion (light circles in FIGS. 11D-11F) and in the anterior, posterior, lateral, and septal wall at 100% occlusion (light circles in FIGS. 11G-11I). In the ischemic cases, the wave was initiated as in the normal case, but its propagation was impeded at the mid-apical level. After EMW propagation, a region that did not undergo thickening could be identified, which indicated an inability of the tissue to contract. The location of the ischemic region is consistent with the pathology findings as shown in FIG. 10I.

FIGS. 12A-12C illustrate electromechanical strain maps at (a) 27 ms, (b) 52 ms and (c) 72 ms after the Q wave of the electrocardiogram in a healthy young human volunteer. They show two waves (arrows) propagating from base (right) to apex (left). The image frames were reconstructed from 5 sectors obtained at 390 frames per second using the motion-matching algorithm detailed above.

FIGS. 13A-13C illustrate images of a pulse wave propagating through the abdominal aorta of a healthy human volunteer. The arrows indicate the propagation of the pulse wave, which is an indicator of the aorta's stiffness. The image frames were reconstructed from seven sectors acquired at 492 frames per second. The time indicated on each frame is measured from the onset of the QRS complex of the electrocardiogram. Light and dark shading indicate upward and downward motion, respectively.

FIGS. 14A-14F illustrate electromechanical wave imaging of a patient undergoing cardiac resynchronization therapy with two different pacing schemes: FIGS. 14A-14C illustrate atrial and bi-ventricular pacing and FIGS. 14D-14F illustrate atrial and left-ventricular pacing. The image frames were reconstructed from five sectors acquired at 300 frames per second with the motion-matching algorithm and allow the detection of different wave propagation patterns (arrows) with different pacing schemes. The time indicated on each frame is measured from the onset of the QRS complex of the electrocardiogram. Light and dark shading indicate upward and downward motion, respectively.

FIG. 15 illustrates a 3D electromechanical strain image generated 250 in accordance with the above-described techniques.

In accordance with the principles of the disclosed subject matter a second experiment was conducted, with the approval of the Institutional Animal Care and Use Committee at Columbia University, on three mongrel dogs of either sex, ranging from 23 to 32 kg in weight. The dogs were prepared as detailed above with respect to the first experiment. In this experiment the dogs' hearts were imaged while the hearts were subject to various pacing schemes. Up-to twelve sonomicrometry crystals with a 2-mm diameter combined with bipolar electrodes were implanted in the ventricles. For endocardial and mid-wall crystals, an 18G (18 gauge) needle was used for insertion. All crystals were maintained in position after placement using silk sutures. Pacing and electrophysiology measurements were performed using the crystals. Recording electrodes were located in the mid-wall along the two-chamber view and pacing electrodes were located on the epicardium along the four-chamber view. Ultrasound measurements were taken in accordance with the techniques detailed above.

FIGS. 16A-16E illustrate the propagation of the electromechanical wave from a pacing lead location in the basal region of the lateral wall (as illustrated by the star in FIG. 16A). The white arrows in FIGS. 16A-16E indicate the propagation direction of the electromechanical wave. FIG. 16F illustrates the activation of the electrocardiogram as the electromechanical wave propagates, with each of the time periods of FIGS. 16A-16E indicated.

FIGS. 17A-17D illustrate isochronal maps of four different pacing schemes in both anterior and posterior views. In each of FIGS. 17A-17D the pacing lead location is indicated with a star. These isochronal maps were obtained by defining the onset of the electromechanical wave as the first time-point following the Q-wave, at which the temporal strain profile crosses zero. In FIGS. 17A, 17B and 17D a unique origin of the electromechanical wave, e.g., the region with the shortest zero-crossing time, can be identified and that region coincides with the position of the pacing lead. In FIG. 17C, when the pacing from the apical region of the antero-lateral wall, the pacing lead was located in the apical region between the two planes. As illustrated in FIGS. 17A-17D, the disclosed subject matter can be used to determine the propagation of the electromechanical wave from the location of a pacing lead.

FIG. 17E illustrates an isochronal map in both anterior and posterior views during sinus rhythm. As illustrated in FIG. 17E, during sinus rhythm complex activation patterns result since activation originates from multiple locations following the Purkinje fiber network.

FIG. 18 illustrates the electromechanical wave onset time versus the time of electrical activation for five different pacing schemes corresponding to those illustrated in FIGS. 17A-17E. The pacing schemes are: Sinus Rhythm (FIG. 17E), left ventricle apical region (LVar; FIG. 17C), left ventricle base (LVb; FIG. 17A), right ventricle apex (RVa; FIG. 17D), and left ventricle apex (LVa; FIG. 17B). The electrical activation data was obtained using four recording electrodes placed in the two-chamber view plane for that purpose. As illustrated in FIG. 18, a linear relationship between the onset of the electromechnical wave and the electrical activation time was found in all four pacing schemes and during sinus rhythm. The linear relationship has a slope of 0.99±0.1 (R²=0.88, p<10⁻⁷) and an intercept of 14±7 ms (p=0.06).

In accordance with the principles of the disclosed subject matter an experiment was conducted on two 23-year-old healthy human subjects; one male, one female. FIG. 19A shows the propagation of the electromechanical wave (outlined in white) in the 23-year-old female at 26.25 ms, 100.26 ms, 210.24 ms, and 240.16 ms. The time of activation in the atria of the subject was defined as the first occurrence following the onset of the P-wave at which the strains in absolute value exceeded 0.025%. Using this definition, the right atrium was activated 30-35 ms following the onset of the P-wave, and the electromechnical activation propagated toward the left atrium. As a result, immediately after the onset of the Q-wave, the ventricles were in a relaxation (or pre-stretched) state. The septum was activated first at the mid-level, and the electromechanical wave propagated towards the apex and base. FIG. 19B illustrates the corresponding isochronal representation of the electromechnical wave in FIG. 19A. As illustrated in FIGS. 19A-19B, the propagation of the electromechanical wave can be imaged using the disclosed techniques in a human subject in vivo.

It will be understood that the foregoing is only illustrative of the principles described herein, and that various modifications can be made by those skilled in the art without departing from the scope and spirit of the disclosed subject matter. For example, the system and methods described herein are used for forming images of tissue displacements and strains. It is understood that that techniques described herein are useful for generating time sequences of tissue displacements and strains and/or other characteristics. Further, the techniques described have been performed on open-chested canines in order to validate with invasive procedures but it is understood the techniques are applicable to non-invasive measurements of cardiac activity. It is further understood that the techniques described herein are applicable to tissue measurements other than the examples given for cardiac tissue. Moreover, features of embodiments described herein can be combined and/or rearranged to create new embodiments. 

We claim:
 1. A method for matching a characteristic of two or more sectors of a moving tissue to verify whether any portions thereof overlap, comprising: acquiring tissue data for at least a first sector and a second sector of said moving tissue; estimating a characteristic of at least a portion of said first sector and a characteristic of at least a portion of said second sector from said acquired tissue data; and matching said estimated characteristic of said portion of said first sector with said estimated characteristic of said portion of said second sector, to verify whether said portion of said first sector overlaps with said portion of said second sector.
 2. The method of claim 1, further comprising determining a time delay between said matched characteristic of said portion of said first sector and said matched characteristic of said portion of said second sector.
 3. The method of claim 2, further comprising forming an image of said matched characteristic of said portion of said first sector and said matched characteristic of said portion of said second sector utilizing said determined time delay.
 4. The method of claim 1, wherein estimating said characteristic further comprises estimating a displacement.
 5. The method of claim 1, wherein estimating said characteristic further comprises estimating a strain.
 6. The method of claim 1, wherein estimating said characteristic further comprises estimating a velocity.
 7. The method of claim 1, wherein estimating said characteristic further comprises estimating a strain rate.
 8. The method of claim 1, wherein estimating said characteristic further comprises estimating a stiffness.
 9. The method of claim 4, wherein said displacement comprises axial displacement.
 10. The method of claim 4, wherein said displacement comprises lateral displacement.
 11. The method of claim 3, wherein forming said image comprises forming a one-dimensional image of said tissue, a two-dimensional image of said tissue, a three-dimensional image of said tissue, or a four-dimensional image of said tissue.
 12. The method of claim 1, wherein estimating said characteristic further comprises using a speckle-tracking technique.
 13. The method of claim 1, further comprising: acquiring electrical activity data from said moving tissue; and determining a correspondence between said electrical activity and said estimated characteristic of said portion of said first sector and said estimated characteristic of said portion of said second sector.
 14. A system for matching a characteristic of two or more sectors of a moving tissue to verify whether any portions thereof overlap, comprising: a computer readable medium storing program instructions; and a processor adapted to receive tissue data for at least a first sector and a second sector of said moving tissue, wherein said processor is operatively connected to said computer readable medium and configured to execute said stored program instructions, wherein said processor is further configured such that upon execution of said stored program instructions, said processor: estimates a characteristic of at least a portion of said first sector and a characteristic of at least a portion of said second sector from said acquired tissue data, and matches said estimated characteristic of said portion of said first sector with said estimated characteristic of said portion of said second sector, to verify whether said portion of said first sector overlaps with said portion of said second sector.
 15. The system of claim 14, wherein said processor is further configured to determine a time delay between said matched characteristic of said portion of said first sector and said matched characteristic of said portion of said second sector.
 16. The system of claim 15, wherein said processor is further configured to form an image of said matched characteristic of said portion of said first sector and said matched characteristic of said portion of said second sector utilizing said determined time delay.
 17. The system of claim 14, further comprising a data acquisition device for acquiring data from two or more sectors of said tissue.
 18. The system of claim 17, wherein said data acquisition device comprises an ultrasound device, an Mill device, or a CT device.
 19. The system of claim 17, wherein said data acquisition device is capable of acquiring data at a rate of up to 10000 frames per second.
 20. The system of claim 14, further comprising an electrical detection device configured to detect an electrical signal propagating through said tissue. 